Sex-Stratified Analysis of MCP-1, CXCL10, MMP-3, and MMP-9 in Relation to Chronic Health Outcomes in Sulfur Mustard Survivors.

BACKGROUND: People exposed to sulfur mustard (SM), experience acute and chronic disorders primarily in the skin, eyes, and respiratory system. Here we examined sex differences in MCP-1, CXCL10, MMP-3, and MMP-9 in SM survivors and unexposed controls with and without definite lung, eye, and skin disorders. METHODS: This research is a part of phase II of the SICS (Sardasht-Iran Cohort Study) and relates to the health screening performed 26 years post-exposure in SM survivors. In total, 489 subjects (361 men and 128 women) with a history of SM exposure, along with 137 age- and sex-matched unexposed controls (93 men and 44 women), constitute the study population. All participants underwent clinical evaluation by expert specialists. Serum concentrations of MCP-1, CXCL10, MMP-3, and MMP-9 were measured using the ELISA technique. RESULTS: SM-exposed individuals showed significantly lower serum CXCL10 levels compared with unexposed controls, while MCP-1 and MMP-9 did not differ significantly at the total population level. MMP-3 also showed no significant unadjusted difference; however, multivariable regression, adjusting for the significant age difference between groups, revealed a significant exposure-associated reduction in MMP-3 (p < 0.001), indicating that age had masked this association in the unadjusted comparison. Sex-stratified analysis revealed that CXCL10 was consistently and significantly lower in both exposed men and women after FDR correction. MMP-3 was significantly higher in men than women, regardless of exposure status, with no significant exposure-related difference surviving FDR correction in either sex. MMP-9 exhibited a sex-dependent exposure effect: levels were significantly elevated in exposed men, whereas the decreasing trend observed in exposed women did not survive FDR adjustment. Among clinicopathological associations, lower MMP-3 was significantly associated with dermatological disorders in SM-exposed subjects. A borderline elevation of MMP-9 was observed in SM-exposed subjects with ocular disorders; however, this association did not survive FDR adjustment and requires cautious interpretation. No significant associations were identified between any biomarker and pulmonary disorders in either group. CONCLUSION: Our findings imply significant disparities in immune responses between men and women, highlighting the complex interplay of sex and chemical exposure on health outcomes.